N‐Methylanilines as Simple and Efficient Promoters for Radical‐Type Cross‐Coupling Reactions of Aryl Iodides

Abstract

Activation of the carbon-halogen bonds in aryl halides is a key step in transition-metal-free cross-coupling reactions. In this paper, a new and efficient radical initiation system for the activation of iodoarenes to produce aryl radicals was discovered, which employs the combination of N-methylanilines and tBuOK. This radical initiation system is robust and versatile, enabling various types of aryl-radical-related reactions.

The Manganese‐Catalyzed Cross‐Coupling Reaction and the Influence of Trace Metals

“…3,5‐Dimethyl‐1,1′‐biphenyl: Table , Entry 6. Prepared from 1‐iodo‐3,5‐dimethylbenzene and phenylmagnesium bromide according to the general procedure.…”

Nickel-Catalyzed Regioselective Hydroamination of Ynamides with Secondary Amines

“…To verify this process, 2a was subjected to the standard reaction conditions with deuterated N -methylaniline 1a - D , and the desired isotope-substituted product 3aa - D was isolated (Scheme ). This showed that the proton for hydroamination came from secondary amines (see the Supporting Information).…”

Aromatization modulates the activity of small organic molecules as promoters for carbon–halogen bond activation

“…Our previous study showed that, N -methylaniline serves as an efficient promoter for the activation of iodoarenes in the presence of t -BuOK, where N -methylanilide anion acts as an electron donor. 7 However, attempts to enable the activation of bromoarene 1a by structural tuning of the N -methylaniline promoter proved unsuccessful ( Scheme 2a ). Although electron-rich anilines exhibited slightly better activities ( 2a–e ), the results were far from satisfactory, and the attachment of an additional aromatic ring to aniline (either as a substituent or as a fused cycle, 2f–h ) with the aim to assist SET by stabilizing the formed N-centered radical, was also useless.…”

“… 1 In addition to stoichiometric metalation 2 or transition-metal catalysis 3 for C–X bond activation, in recent years the development of small-organic-molecule-promoted C–X bond activation has attracted great attention. A series of small organic molecules, such as 1,10-phenanthrolines, 4 1,2-diamines, 5 1,2-diols 6 and N -methylanilines, 7 were found to promote the activation of haloarene in the presence of a base, producing a reactive aryl radical intermediate which undergoes substitution processes (referred to as base-promoted homolytic aromatic substitution, BHAS). 8 Careful mechanistic studies revealed that the promoter is transformed into a “super electron donor” under the reaction conditions, which then initiates the cleavage of the C–X bond by single electron transfer (SET) to the haloarene substrate ( Scheme 1a ).…”